Abstract

Inspired by recent proteomic data demonstrating the upregulation of carbon and glycogen metabolism in aging human hematopoietic stem and progenitor cells (HPCs, CD34+ cells), this report addresses whether this is caused by elevated glycolysis of the HPCs on a per cell basis, or by a subpopulation that has become more glycolytic. The average glycogen content in individual CD34+ cells from older subjects (> 50 years) was 3.5 times higher and more heterogeneous compared to younger subjects (< 35 years). Representative glycolytic enzyme activities in HPCs confirmed a significant increase in glycolysis in older subjects. The HPCs from older subjects can be fractionated into three distinct subsets with high, intermediate, and low glucose uptake (GU) capacity, while the subset with a high GU capacity could scarcely be detected in younger subjects. Thus, we conclude that upregulated glycolysis in aging HPCs is caused by the expansion of a more glycolytic HPC subset. Since single-cell RNA analysis has also demonstrated that this subpopulation is linked to myeloid differentiation and increased proliferation, isolation and mechanistic characterization of this subpopulation can be utilized to elucidate specific targets for therapeutic interventions to restore the lineage balance of aging HPCs.

Details

Title
Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells
Author
Poisa-Beiro Laura 1 ; Thoma, Judith 2 ; Landry, Jonathan 3 ; Sauer, Sven 4 ; Yamamoto Akihisa 5 ; Eckstein Volker 6 ; Romanov, Natalie 7 ; Raffel, Simon 6 ; Hoffmann, Georg F 4 ; Bork Peer 8 ; Benes, Vladimir 3 ; Anne-Claude, Gavin 9 ; Tanaka Motomu 2 ; Ho, Anthony D 10 

 Heidelberg University, Department of Medicine V, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373); EMBL and Heidelberg University, Molecular Medicine Partnership Unit Heidelberg, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X) 
 Heidelberg University, Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373); Kyoto University, Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
 European Molecular Biology Laboratory (EMBL), Genomics Core Facility, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X) 
 University Hospital Heidelberg, Division of Child Neurology and Metabolic Diseases, Centre for Child and Adolescent Medicine, Heidelberg, Germany (GRID:grid.5253.1) (ISNI:0000 0001 0328 4908) 
 Kyoto University, Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
 Heidelberg University, Department of Medicine V, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
 European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X); Max Planck Institute of Biophysics, Frankfurt am Main, Germany (GRID:grid.419494.5) (ISNI:0000 0001 1018 9466) 
 EMBL and Heidelberg University, Molecular Medicine Partnership Unit Heidelberg, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X); European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X) 
 EMBL and Heidelberg University, Molecular Medicine Partnership Unit Heidelberg, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X); European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X); University of Geneva, Department for Cell Physiology and Metabolism, Centre Medical Universitaire, Geneva 4, Switzerland (GRID:grid.8591.5) (ISNI:0000 0001 2322 4988) 
10  Heidelberg University, Department of Medicine V, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373); EMBL and Heidelberg University, Molecular Medicine Partnership Unit Heidelberg, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X); Kyoto University, Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2423651703
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.